Division of Infection and Immunity, Rayne Institute, University College London, London, UK.
Virus Res. 2013 Sep;176(1-2):1-15. doi: 10.1016/j.virusres.2013.05.007. Epub 2013 May 28.
Our work over the past eight years has focused on the use of HIV-1 lentiviral vectors (lentivectors) for the genetic modification of dendritic cells (DCs) to control their functions in immune modulation. DCs are key professional antigen presenting cells which regulate the activity of most effector immune cells, including T, B and NK cells. Their genetic modification provides the means for the development of targeted therapies towards cancer and autoimmune disease. We have been modulating with lentivectors the activity of intracellular signalling pathways and co-stimulation during antigen presentation to T cells, to fine-tune the type and strength of the immune response. In the course of our research, we have found unexpected results such as the surprising immunosuppressive role of anti-viral signalling pathways, and the close link between negative co-stimulation in the immunological synapse and T cell receptor trafficking. Here we review our major findings and put them into context with other published work.
在过去的八年中，我们的工作重点是利用 HIV-1 慢病毒载体（慢病毒）对树突状细胞（DC）进行基因修饰，以控制其在免疫调节中的功能。DC 是关键的专业抗原呈递细胞，可调节包括 T、B 和 NK 细胞在内的大多数效应免疫细胞的活性。它们的基因修饰为开发针对癌症和自身免疫性疾病的靶向治疗提供了手段。我们一直在使用慢病毒调节抗原呈递给 T 细胞过程中的细胞内信号通路和共刺激的活性，以微调免疫反应的类型和强度。在我们的研究过程中，我们发现了一些意外的结果，例如抗病毒信号通路的惊人免疫抑制作用，以及免疫突触中的负共刺激与 T 细胞受体运输之间的紧密联系。在这里，我们回顾了我们的主要发现，并将其与其他已发表的工作联系起来。
